Unraveling the functional significance of regulatory variation across the human genome
Abstract/Contents
- Abstract
- Understanding the relationship between genotype and phenotype remains one of the greatest challenges in genetics and medicine today. Recently, a wealth of new genomic and functional data has enabled researchers to catalog human genetic variation, characterize their effects on phenotypic variation, and test hypotheses to uncover their underlying mechanisms. Despite these achievements, basic questions about genetic variants remain unanswered, including their full distribution of effects on heritability, their molecular mechanisms of action, and their interaction with environmental variables. Resolving these questions will improve our resolution of the genetic architecture of phenotypic traits and uncover the molecular basis of human disease. This thesis begins to address these questions by dissecting the role of genetic variants on regulatory variation across tissues and individuals. First, Chapter 1 provides a broad introduction to key biological and technological concepts that form the basis of the work presented in this dissertation. Then, Chapter 2 offers a detailed discussion of the experimental and analytical methods utilized to interrogate regulatory variation. Next, Chapter 3 assesses transcriptomic variation across ten tissues of the human body, with a particular focus on patterns of allele-specific expression for deleterious variation. Lastly, Chapter 4 explores differences in regulatory variation between the sexes with a focus on contributions from the X chromosome and potential mechanisms. Together, these chapters provide insight into the impact and mechanistic basis of regulatory variation across tissues and across the sexes.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2015 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Kukurba, Kimberly R |
|---|---|
| Associated with | Stanford University, Department of Genetics. |
| Primary advisor | Montgomery, Stephen, 1979- |
| Primary advisor | Snyder, Michael, Ph. D |
| Thesis advisor | Montgomery, Stephen, 1979- |
| Thesis advisor | Snyder, Michael, Ph. D |
| Thesis advisor | Fraser, Hunter B |
| Thesis advisor | Pritchard, Jonathan D |
| Thesis advisor | Sidow, Arend |
| Advisor | Fraser, Hunter B |
| Advisor | Pritchard, Jonathan D |
| Advisor | Sidow, Arend |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Kimberly R. Kukurba. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2015. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2015 by Kimberly Rebecca Kukurba
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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